目的:探讨化瘀导滞汤对庆大霉素所致的肾间质纤维化的影响及作用机制。方法:32只健康雄性Wistar大鼠随机分为3组:正常组(6只)、肾纤维化模型组(13只)、化瘀导滞汤治疗组(13只)。肾纤维化模型组和化瘀导滞汤治疗组给予庆大霉素造成肾纤维化,造模同时,治疗组给予化瘀导滞汤煎剂灌胃干预,直至取材。于造模后30d取材,光镜下观察肾组织形态学改变,计算肾系数、检测血肌酐、血尿素氮、24h尿蛋白总量,检测各组大鼠肾组织α-平滑肌肌动蛋白(α-SMA)、Smad通路蛋白2(Smad2)、Smad通路蛋白7(Smad7)的表达水平。结果:肾纤维化模型组大鼠与正常组比较,光镜下可见肾小管上皮细胞以坏死为主,部分变性,肾小管萎缩和扩张,间质中有成纤维细胞增生和炎症细胞浸润,间质明显增宽。模型组肾系数、血肌酐、血尿素氮、24h尿蛋白总量明显高于正常组(P〈0.01),α-SMA、Smad2蛋白表达明显高于正常组(P〈0.01),Smad7蛋白表达明显低于正常组(P〈0.01);化瘀导滞汤治疗组与肾纤维化模型组比较,光镜下肾小管结构有明显改善,治疗组肾系数、血肌酐、血尿素氮、24h尿蛋白总量与模型组比较有显著下降(P〈0.01),治疗组α-SMA、Smad2蛋白表达明显低于模型组(P〈0.01),Smad7蛋白表达无明显变化(P〉0.05)。结论:化瘀导滞汤有良好的防治庆大霉素诱导的肾纤维化作用。
AIM: To investigate the effects of Hua Yu Dao Zhi decoction (HYDZD) on renal interstitial fibrosis induced by gentamicin in rats. METHODS: 32 healthy male Wistar rats were randomly divided into 3 groups: control group ( n = 6 ), gentamicin group ( n = 13 ) and HYDZD + gentamicin group ( n = 13 ). The renal tubulointerstitial fibrosis in rats was induced by gentamicin for 9 d. All rats were sacrificed on 30 d after modeling and renal tissues were stained with HE. The renal indexes were calculated and the changes of serum creatinine, blood urea nitrogen, total urinary protein in 24 h, and the level of α - SMA, Smad2, Smad7 were detected. RESULTS : Compared to control group, it was observed that there was mainly necrosis and partly degeneration in the renal tubular epithelial cells, proliferation of fibroblasts and infiltration of the inflammatory cells in the interstitial substance in gentamicin group under the light microscope. The renal indexes, serum creatinine, blood urea nitrogen, total urinary protein in 24 h, and the level of α- SMA, Smad2 were significantly higher than those in control group (P 〈0. 01 ) and the level of Smad7 was significantly lower than that in control group (P 〈 0.01). Under the light microscope, the results of all mentioned above in HYDZD + gentamicin group were improved significantly (P 〈 0. 01 ), the level of α - SMA, Smad2 were significantly lower than those in gentamicin group (P 〈0. 01). However, no significant difference of Smad7 protein expression between gentamicin group and HYDZD + gentamicin group was observed ( P 〉 0. 05 ). CONCLUSION : HYDZD is very effective in preventing and treating renal interstitial fibrosis caused by gentamicin with the decreased level of Smad2.